OVERVIEW: What every practitioner needs to know

Are you sure your patient has measles? What are the typical findings for this disease?

Fever

The three "Cs": cough, coryza, and conjunctivitis

Erythematous maculopapular rash, beginning on the head and spreading to involve the trunk and extremities

Koplik spots (small white papules) seen on the buccal mucosa before the onset of rash

What other disease/condition shares some of these symptoms?

Rubella

Enterovirus infection

Roseola

Scarlet fever

Dengue virus infection

What caused this disease to develop at this time?

Exposure to an infectious person with measles

Lack of protective immunity after measles vaccination or before measles virus infection

Undernourished and immunocompromised persons are at increased risk of severe disease

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Serologic test for measles IgM antibodies

A positive test indicates acute measles virus infection.

False-negative tests may result if testing is done within 72 hours of rash onset. If measles is suspected, the test should be repeated.

Measles IgM antibodies may be detectable for a month after onset of rash.

Would imaging studies be helpful? If so, which ones?

A chest radiograph may be useful in the management of the child with measles and suspected pneumonia.

If you are able to confirm that the patient has measles, what treatment should be initiated?

Treatment of uncomplicated measles is symptomatic and includes bed rest, hydration, and antipyretic agents.

The World Health Organization recommends administration of two daily doses of 200,000 IU of vitamin A to children with measles who are 12 months of age or older, 100,000 IU is recommended for children 6-12 months of age, and 50,000 IU for children younger than 6 months of age.

The American Academy of Pediatrics recommends that vitamin A supplementation be considered in children 6 months to 2 years of age who are hospitalized with measles or its complications.

A third dose of vitamin A is recommended 2-4 weeks later in children with clinical evidence of vitamin A deficiency.

Bacterial complications of measles, such as pneumonia, should be treated with antibiotics.

What are the adverse effects associated with each treatment option?

The safety of vitamin A supplementation in children younger than 6 months of age is not well established, although measles in this age group is associated with high mortality.

What are the possible outcomes of this disease?

Most children with uncomplicated measles recover without sequelae. Children who are undernourished (particularly those with vitamin A deficiency) and children who are immunocompromised are at greater risk of complications and mortality. Approximately 1/1000 otherwise healthy indviduals with measles acquire an autoimmune encephalitis.

The risks of vitamin A supplementation are minimal and the benefits far outweigh the risks.

What causes this disease and how frequent is it?

Measles is caused by the measles virus. This virus is one of the most highly contagious, directly transmitted pathogens, and outbreaks can occur in populations in which fewer than 10% of persons are susceptible.

Measles virus is transmitted by direct person-to-person transmission through the respiratory route (droplet or airborne transmission).

Persons with measles are infectious 3-5 days before the onset of rash and about 4 days after the onset of rash.The incubation period for measles is about 10 days to onset of symptoms and 14 days to onset of rash.

In temperate climates, measles transmission peaks in late winter and early spring.

The average age of contraction of measles depends on the intensity of transmision: younger children are infected when transmission intensity is high, population density is high, and vaccine coverage is low. As vaccination coverage and thus population immunity increases, the age distribution of cases may be shifted into adolescence and adulthood.

Infants become susceptible to measles virus infection when passively acquired maternal antibody is lost. Infants born to women with vaccine-induced immunity become susceptible to measles at a younger age than those born to women with naturally acquired immunity. Case fatality is highest in infants and undernourished children, particularly those with vitamin A deficiency.

How do these pathogens/genes/exposures cause the disease?

Respiratory droplets from infected persons serve as vehicles of transmission by delivering infectious virus to the respiratory tract mucosa of susceptible hosts.

During the incubation period, measles virus replicates and spreads within the infected host.

Viral replication occurs initially in epithelial cells in the upper respiratory tract and the virus spreads to local lymphatic tissue. Replication in local lymph nodes is followed by viremia and the dissemination of measles virus to many organs, including lymph nodes, skin, kidney, gastrointestinal tract, and liver.

Host immune responses at sites of virus replication are responsible for the signs and symptoms of measles. Host immune responses to measles virus are essential for viral clearance, clinical recovery, and the establishment of long-term immunity.

Other clinical manifestations that might help with diagnosis and management

Immunocompromised persons with impaired cellular immunity, including children infected with human immunodeficiency virus (HIV), may not have the characteristic measles rash, hindering clinical diagnosis.

What complications might you expect from the disease or treatment of the disease?

The respiratory tract is a frequent site of complication, with pneumonia accounting for most measles-associated deaths. Pneumonia is caused by secondary viral or bacterial infections or, in immunocompromised persons, by measles virus itself resulting in a giant cell pneumonitis. Other respiratory complications include laryngotracheobronchitis (croup) and otitis media.

Mouth ulcers, or stomatitis, may hinder children from eating or drinking. Some children with measles have diarrhea, contributing to undernutrition.

Keratoconjunctivitis can occur after measles, particularly in children with vitamin A deficiency, and was a frequent cause of blindness in the past.

Death occurs in about 1 in every 1000 cases in the United States, but the case fatality ratio can be greater than 10% in undernourished children with poor access to health care.

Encephalomyelitis after measles complicates approximately 1/1000 cases. Encephalomyelitis is an autoimmune phenomenon that occurs within 2 weeks of the onset of rash and is characterized by fever, seizures, and a variety of neurologic abnormalities.

Measles inclusion body encephalitis (MIBE) is a rare but fatal complication associated with progressive neurologic deterioration that affects individuals with defective cellular immunity and typically occurs months after infection. MIBE has been described in children who have had renal and stem cell transplantation and may be an outcome of measles in HIV-infected persons.

Subacute sclerosing panencephalitis (SSPE) is a rare delayed complication of measles that occurs in approximately 1/100,000-1/10,000 cases and is characterized by seizures and progressive deterioration of cognitive and motor functions, followed by death 5-15 years after measles virus infection. SSPE most often occurs in persons infected with measles virus before the age of 2 years.

Are additional laboratory studies available; even some that are not widely available?

How can this disease be prevented?

The best means of preventing measles is with active immunization with measles vaccine. The World Health Organization recommends the first dose of measles vaccine be administered at 9 months of age. The American Academy of Pediatrics recommends the first dose of measles vaccine be administered at 12-15 months of age.

Primary vaccine failure occurs in 15% of children vaccinated at 9 months of age, in 5% of children vaccinated at 12 months of age, and in 2% of children vaccinated at 15 months of age. Maternal antibodies and immunologic immaturity are responsible for primary vaccine failure in infancy.

A second dose of measles vaccine is needed to achieve high levels of population immunity and interrupt measles virus transmission. The American Academy of Pediatrics recommends the second dose of measles vaccine be administered before school at 4-6 years of age. In many countries, children receive their second dose of measles vaccine through periodic mass vaccination campaigns called supplementary immunization activities.

Immune globulin (0.25 mL/kg) can be given to prevent or attenuate measles in susceptible persons within 6 days of exposure. Immunocompromised children should receive 0.5 mL/kg. The maximum dose of immune globulin is 15 mL.

Undernutrition, and specifically vitamin A deficiency, is a risk factor for mortality from measles. Proper nutrition and vitamin A supplementation can reduce measles mortality in children at risk.

What is the evidence?

A Cochrane Review found that two doses of vitamin A (200,000 IU) on consecutive days was associated with a reduction in the risk of mortality in children younger than 2 years of age (relative risk [RR], 0.18; 95% confidence interval [CI], 0.03-0.61) and a reduction in the risk of pneumonia-specific mortality (RR, 0.33; 95% CI, 0.08-0.92).

Ongoing controversies regarding etiology, diagnosis, treatment

Ribavirin has been used to treat immunocompromised persons and those with severe measles, but no controlled trials have demonstrated efficacy. Ribavarin is not approved by the US Food and Drug Administration to treat persons with measles.

Low measles vaccine coverage is responsble for measles outbreaks. Some parents refuse measles vaccination for their children because of an erroneous belief that measles vaccine is associated with autism. Numerous studies have shown no association between measles vaccine and autism, and the original study making that claim was discredited.